PROJECT SUMMARY/ABSTRACT The use of language in everyday life requires the participation of numerous regions of the brain as well as the intricate web of fiber pathways that connect them. The study of language and language disorders has largely focused on the contributions of these cortical regions in supporting speech and language functions, while the role of the underlying tracts, which could play a major role in language processing is largely unknown. While some "disconnection" syndromes have been described, the result of injury to some of the major fiber tracts in the brain has not been well studied. This has been due primarily to the difficulty in isolating these tracts with traditional neuroimaging tools, thus identifying those tracts that have been damaged over those that have been spared. In addition, recruiting the large sample of brain-injured patients required to obtain both the necessary imaging and behavioral data takes a great deal of time and resources. The goal of this project is to evaluate the contributions of major pathways of the brain that must play a role in language processing by examining the effects of damage to these pathways. This will be done through extensive evaluation of 60 chronic brain-injured patients with aphasia due to stroke, whose language and neuropsychological deficits will be thoroughly evaluated by our staff at the Center for Aphasia and Related Disorders. We will employ the latest techniques in imaging the fiber pathways of the brain, using diffusion tensor imaging (DTI) and diffusion spectrum imaging (DSI) with these patients to image the fiber pathways of the brain, obtain measurements of tract integrity, and perform tractography that visualizes the actual fiber pathways in each patient. The combined use of these behavioral data, the DTI and DSI results from the same patients, as well as voxel-based lesion-symptom mapping (VLSM) analyses will allow us the best possible evaluation of the role of these pathways in language functioning. Understanding the effects of brain injury to the language system is key to the accurate diagnosis and treatment of the language disorders that affect our veteran patients. Knowing how lesions to the cortex and to the underlying fiber tracts each affect the different components of language can help clinicians, patients and caregivers to understand the effect the injury has had on the patient's communication skills. Different disorders require different treatments, and thus more accurate diagnoses naturally lead to more effective remediation. We have already seen that damage to cortical areas, that cannot be replaced, responds differently to treatment than does damage to a fiber tract that can potentially be circumnavigated. With neuroimaging data now routinely available on patients in VA medical facilities, the information gleaned from this project can be applied directly to the veteran patients we serve, thus providing them with the optimum in diagnostic and rehabilitative care, not to mention hope for a better recovery. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE Brain injury is very common in our veteran patients and one of its unfortunate consequences can be the disruption of speech and language skills (aphasia) that affect how people can communicate. While some research has been dedicated to understanding these problems and how they relate to injuries in different parts of the brain, very little has been done to understand how language skills can be affected by damage to the fiber pathways that connect these brain regions to one another. This research will use state-of-the- art brain imaging tools to understand how communication skills are affected after injury to fiber tract pathways and how this damage interacts with other parts of the brain. Such information provides the best information to clinicians whose mission is to give our veteran patients the most accurate diagnosis and most effective treatments. This knowledge also helps our patients and their caregivers to understand the injury and how they can best cope with the changes in their ability to communicate.